A comparative study of radiolabeled bombesin analogs for the PET imaging of prostate cancer.

Abstract

UNLABELLED:

Radiolabeled bombesin (BBN) analogs that bind to the gastrin-releasing peptide receptor (GRPR) represent a topic of active investigation for the development of molecular probes for PET or SPECT of prostate cancer (PCa). RM1 and AMBA have been identified as the 2 most promising BBN peptides for GRPR-targeted cancer imaging and therapy. In this study, to develop a clinically translatable BBN-based PET probe, we synthesized and evaluated (18)F-AlF- (aluminum-fluoride) and (64)Cu-radiolabeled RM1 and AMBA analogs for their potential application in PET imaging of PCa.

METHODS:

1,4,7-triazacyclononane, 1-glutaric acid-4,7 acetic acid (NODAGA)-conjugated RM1 and AMBA were synthesized and tested for their GRPR-binding affinities. The NODAGA-RM1 and NODAGA-AMBA probes were further radiolabeled with (64)Cu or (18)F-AlF and then evaluated in a subcutaneous PCa xenograft model (PC3) by small-animal PET imaging and biodistribution studies.

RESULTS:

NODAGA-RM1 and NODAGA-AMBA can be successfully synthesized and radiolabeled with (64)Cu and (18)F-AlF. (64)Cu- and (18)F-AlF-labeled NODAGA-RM1 demonstrated excellent serum stability and tumor-imaging properties in the in vitro stability assays and in vivo imaging studies. (64)Cu-NODAGA-RM1 exhibited tumor uptake values of 3.3 ± 0.38, 3.0 ± 0.76, and 3.5 ± 1.0 percentage injected dose per gram of tissue (%ID/g) at 0.5, 1.5, and 4 h after injection, respectively. (18)F-AlF-NODAGA-RM1 exhibited tumor uptake values of 4.6 ± 1.5, 4.0 ± 0.87, and 3.9 ± 0.48 %ID/g at 0.5, 1, and 2 h, respectively.

CONCLUSION:

The high-stability, efficient tumor uptake and optimal pharmacokinetic properties highlight (18)F-AlF-NODAGA-RM1 as a probe with great potential and clinical application for the PET imaging of prostate cancer.

• Authors: Yang Liu, Xiang Hu, Hongguang Liu, Lihong Bu, Xiaowei Ma, Kai Cheng, Jinbo Li, Mei Tian, Hong Zhang, Zhen Cheng
• Journal: Journal of nuclear medicine : official publication, Society of Nuclear Medicine (J Nucl Med) Vol. 54 Issue 12 Pg. 2132-8 (Dec 2013) ISSN: 1535-5667 [Electronic] United States
• PMID: 24198391 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• 1-(1,3-carboxypropyl)-4,7-carboxymethyl-1,4,7-triazacyclononane
• Acetates
• Copper Radioisotopes
• Fluorine Radioisotopes
• Heterocyclic Compounds, 1-Ring
• Bombesin

Topics

• Acetates (chemistry)
• Animals
• Bombesin (analogs & derivatives, blood, pharmacokinetics)
• Cell Line, Tumor
• Cell Transformation, Neoplastic
• Copper Radioisotopes
• Drug Stability
• Fluorine Radioisotopes
• Heterocyclic Compounds, 1-Ring (chemistry)
• Isotope Labeling
• Male
• Mice
• Positron-Emission Tomography (methods)
• Prostatic Neoplasms (diagnostic imaging, pathology)
• Radiochemistry